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Moderate Ethanol Pretreatment Mitigates ICH-induced Injury via ER Stress Modulation in Rats
Frontiers in Molecular Neuroscience ( IF 3.5 ) Pub Date : 2021-05-26 , DOI: 10.3389/fnmol.2021.682775
Peter Bor-Chian Lin , Po-Kai Wang , Cheng-Yoong Pang , Wei-Fen Hu , Andy Po-Yi Tsai , Adrian L. Oblak , Hock-Kean Liew

Intracerebral hemorrhage (ICH) is a life-threatening type of stroke that disrupts the normal neurological function of the brain. Clinical studies have reported a non-linear J-shaped association between alcohol consumption levels and the occurrence of cerebral stroke. Specifically, alcohol intoxication increases stroke incidence, while moderate alcohol pre-conditioning decreases stroke frequency and improves outcomes. Although alcohol pre-consumption is likely a crucial player in ICH, the underlying mechanism remains unclear. We performed 1-hour alcohol pre-conditioning followed by ICH induction in Sprague Dawley (SD) rats to investigate the role of alcohol pre-conditioning in ICH. Interestingly, behavioral test analysis found that ethanol intoxication (3 g/kg) aggravated ICH-induced neurological deficits, but moderate ethanol pre-conditioning (0.75 g/kg) ameliorated ICH-induced neurological deficits by reducing the oxidative stress and proinflammatory cytokines release. Moreover, we found that moderate ethanol pretreatment improved the striatal ER homeostasis by increasing the chaperone protein expression and reducing oxidative stress and apoptosis caused by ICH. Our findings show that the mechanism regulated by moderate ethanol pre-conditioning might be beneficial for ICH, indicating the importance of ER homeostasis, oxidative stress, and differential cytokines release in ICH.

中文翻译:

中度乙醇预处理可通过内质网应激调节减轻大鼠脑出血

脑出血(ICH)是威胁生命的一种中风,会破坏大脑的正常神经功能。临床研究报告了饮酒量与脑卒中发生之间呈非线性J型关系。具体而言,酒精中毒会增加中风发生率,而适度的酒精预处理会降低中风发生率并改善结局。尽管饮酒可能是ICH的关键因素,但其潜在机制仍不清楚。我们在Sprague Dawley(SD)大鼠中进行了1小时的酒精预处理,然后进行了ICH诱导,以研究酒精预处理在ICH中的作用。有趣的是,行为测试分析发现乙醇中毒(3 g / kg)加重了ICH诱导的神经功能缺损,但适度的乙醇预处理(0。75 g / kg)通过减少氧化应激和促炎性细胞因子释放,减轻了ICH引起的神经功能缺损。此外,我们发现适度的乙醇预处理可通过增加分子伴侣蛋白的表达并减少由ICH引起的氧化应激和细胞凋亡来改善纹状体ER稳态。我们的发现表明,适度乙醇预处理调节的机制可能对ICH有益,表明ER稳态,氧化应激和ICH中差异性细胞因子释放的重要性。我们发现适度的乙醇预处理可通过增加分子伴侣蛋白的表达并减少由ICH引起的氧化应激和细胞凋亡来改善纹状体ER稳态。我们的发现表明,适度乙醇预处理调节的机制可能对ICH有益,表明ER稳态,氧化应激和ICH中差异性细胞因子释放的重要性。我们发现适度的乙醇预处理可通过增加分子伴侣蛋白的表达并减少由ICH引起的氧化应激和细胞凋亡来改善纹状体ER稳态。我们的发现表明,适度乙醇预处理调节的机制可能对ICH有益,表明ER稳态,氧化应激和ICH中差异性细胞因子释放的重要性。
更新日期:2021-05-26
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